| First Author | Garcia AG | Year | 2012 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 303 |
| Issue | 5 | Pages | H587-96 |
| PubMed ID | 22730392 | Mgi Jnum | J:189195 |
| Mgi Id | MGI:5444593 | Doi | 10.1152/ajpheart.00298.2012 |
| Citation | Garcia AG, et al. (2012) Interferon-gamma ablation exacerbates myocardial hypertrophy in diastolic heart failure. Am J Physiol Heart Circ Physiol 303(5):H587-96 |
| abstractText | Diastolic heart failure (HF) accounts for up to 50% of all HF admissions, with hypertension being the major cause of diastolic HF. Hypertension is characterized by left ventricular (LV) hypertrophy (LVH). Proinflammatory cytokines are increased in LVH and hypertension, but it is unknown if they mediate the progression of hypertension-induced diastolic HF. We sought to determine if interferon-gamma (IFNgamma) plays a role in mediating the transition from hypertension-induced LVH to diastolic HF. Twelve-week old BALB/c (WT) and IFNgamma-deficient (IFNgammaKO) mice underwent either saline (n = 12) or aldosterone (n = 16) infusion, uninephrectomy, and fed 1% salt water for 4 wk. Tail-cuff blood pressure, echocardiography, and gene/protein analyses were performed. Isolated adult rat ventricular myocytes were treated with IFNgamma (250 U/ml) and/or aldosterone (1 muM). Hypertension was less marked in IFNgammaKO-aldosterone mice than in WT-aldosterone mice (127 +/- 5 vs. 136 +/- 4 mmHg; P < 0.01), despite more LVH (LV/body wt ratio: 4.9 +/- 0.1 vs. 4.3 +/- 0.1 mg/g) and worse diastolic dysfunction (peak early-to-late mitral inflow velocity ratio: 3.1 +/- 0.1 vs. 2.8 +/- 0.1). LV ejection fraction was no different between IFNgammaKO-aldosterone vs. WT-aldosterone mice. LV end systolic dimensions were decreased significantly in IFNgammaKO-aldosterone vs. WT-aldosterone hearts (1.12 +/- 0.1 vs. 2.1 +/- 0.3 mm). Myocardial fibrosis and collagen expression were increased in both IFNgammaKO-aldosterone and WT-aldosterone hearts. Myocardial autophagy was greater in IFNgammaKO-aldosterone than WT-aldosterone mice. Conversely, tumor necrosis factor-alpha and interleukin-10 expressions were increased only in WT-aldosterone hearts. Recombinant IFNgamma attenuated cardiac hypertrophy in vivo and modulated aldosterone-induced hypertrophy and autophagy in cultured cardiomyocytes. Thus IFNgamma is a regulator of cardiac hypertrophy in diastolic HF and modulates cardiomyocyte size possibly by regulating autophagy. These findings suggest that IFNgamma may mediate adaptive downstream responses and challenge the concept that inflammatory cytokines mediate only adverse effects. |
